Essential regions of the lipopolysaccharide of Pseudomonas aeruginosa responsible for pyrogenicity and activation of the proclotting enzyme of horseshoe crabs. Comparison with antitumor, interferon-inducing and adjuvant activities.
Regions of lipopolysaccharide derived from Pseudomonas aeruginosa essential for pyrogenicity and activation of the proclotting enzyme of the horseshoe crab were examined. Free lipid A with intact fatty acids showed strong pyrogenicity but showed little activation of the proclotting enzyme. Chemical modification of the polysaccharide portion and deacylation of the lipopolysaccharide diminished activation of the proclotting enzyme. The native-protein portion attached to the lipopolysaccharide also inhibited the activation of proclotting enzyme by lipopolysaccharide, but not pyrogenicity. These results indicate that free lipid A is sufficient for pyrogenicity, whereas the complete lipopolysaccharide is the strongest activator of the proclotting enzyme. The lipopolysaccharide of P. aeruginosa, which showed the strongest activation of proclotting enzyme, showed the weakest pyrogenicity of all the lipopolysaccharides tested here. All these results demonstrate that there is not correlation between pyrogenicity and proclotting enzyme activation induced by lipopolysaccharides.
D000818:Animals; D000970:Antineoplastic Agents; D001779:Blood Coagulation Factors / Q000378:metabolism*; D010450:Endopeptidases; D004789:Enzyme Activation; D004792:Enzyme Precursors; D006737:Horseshoe Crabs / Q000201:enzymology; D007369:Interferon Inducers; D008050:Lipid A / Q000302:isolation & purification; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000627:therapeutic use; D011550:Pseudomonas aeruginosa / Q000032:analysis*; D011749:Pyrogens; D011817:Rabbits; D012486:Salmonella typhimurium / Q000032:analysis; D013045:Species Specificity
D000970:Antineoplastic Agents; D001779:Blood Coagulation Factors; D004792:Enzyme Precursors; D007369:Interferon Inducers; D008050:Lipid A; D008070:Lipopolysaccharides; D011749:Pyrogens; D010450:Endopeptidases; C014775:pro-clotting enzyme